This study investigated the anti-wrinkle and anti-inflammatory effects of horse bone hydrolysates of < 3 kDa (HL) and topically applied horse oil (HO) on UVB-induced photoaging and inflammation in hairless mice. Forty-nine mice were divided into seven groups: - NC, chow without UVB irradiation; + UC, chow with UVB irradiation, + HLL, chow with low dose (500 mg/kg body weight (BW)) HL and UVB irradiation; + HLH, chow with high dose (1000 mg/kg BW) HL and UVB irradiation; + HO, chow and combined with topical application of HO and UVB irradiation; + HOHLL, treated with a combination of dietary HLL and topical application of HO with UVB irradiation; + HOHLH, treated with a combination of dietary HLH and topical application of HO with UVB irradiation. The transepidermal water loss in mice of all treatment groups was lower than that of mice in the + UC group. Furthermore, the wrinkle depth in the + HLH group was significantly lower than that in the + UC group. In addition, HO and low level of HL significantly decreased the level of tumor necrosis factor-alpha, interleukin-6, and matrix metalloproteinase-9, thereby down-regulating inflammation, including the cyclooxygenase-2 synthesis. In the future, human trials are needed to confirm the efficacy and synergistic effect of HL and HO.